5-FU-miR-129

5-FU-miR-129 (also known as Mimic-1) is an experimental anticancer RNA therapeutic developed by Curamir Therapeutics in collaboration with Stony Brook University. It consists of a synthetic, double-stranded microRNA-129 (miR-129) mimic where the uracil residues in the guide strand are chemically substituted with 5-fluorouracil (5-FU). This unique modification is designed to enhance the molecule's stability and cytotoxicity while facilitating vehicle-free cellular uptake. As a miR-129 replacement therapy, it functions as a potent tumor suppressor by downregulating multiple oncogenic and survival pathways, specifically targeting transcripts such as BCL2, HMGB1, and E2F3. This leads to G1 cell-cycle arrest and the induction of apoptosis and autophagy. Additionally, the intracellular release of 5-FU metabolites from the mimic inhibits thymidylate synthase, providing a secondary cytotoxic mechanism. The drug is being developed to overcome drug resistance in colorectal cancer and non-small cell lung cancer, including populations resistant to standard chemotherapy and tyrosine kinase inhibitors.

Other names

5-fluorouracil-modified microRNA-129 mimic5-FU-modified miR-129